FDA Approves Kalydeco (ivacaftor) as First and Only CFTR Modulator to Treat Eligible Infants with CF as Early as Six Months of Age

In continuation of my update on Kalydeco (ivacaftor) 

Vertex Pharmaceuticals Incorporated  announced the U.S. Food and Drug Administration (FDA) approved Kalydeco (ivacaftor) for use in children with cystic fibrosis (CF) ages six months to less than 12 months who have at least one mutation in their cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to Kalydeco based on clinical and/or in vitro assay data. Kalydeco is already approved in the U.S., Canada and EU for the treatment of CF in patients ages 12 months and older.

“Today’s approval for Kalydeco allows physicians to begin treating the underlying cause of CF in eligible infants as young as six months of age for the first time, with the potential to modify the course of the disease,” said Margaret Rosenfeld, M.D., MPH, Seattle Children’s Research Institute and Department of Pediatrics, University of Washington School of Medicine.

This FDA approval is based on data from a 24-week Phase 3 open-label safety cohort (ARRIVAL) of 11 children with CF aged six months to less than 12 months who have one of 10 mutations in the CFTR gene (G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D or R117H). The study demonstrated a safety profile similar to that observed in previous Phase 3 studies of older children and adults; most adverse events were mild or moderate in severity, and no patient discontinued therapy due to adverse events. The most common adverse events (≥30%) were cough (64%), nasal congestion (36%) and rhinorrhea (36%). Three serious adverse events, all considered unrelated to study treatment by the investigators, were observed in three patients.

Mean baseline sweat chloride for the children in this cohort was 101.5 mmol/L (n=11). Following 24 weeks of treatment with Kalydeco, the mean sweat chloride level was 43.1 mmol/L (n=6). In the six subjects with paired sweat chloride samples at baseline and week 24, there was a mean absolute change of -58.6 mmol/L (95% CI; -75.9, -41.3).

Results of this study were presented at the 32nd Annual North American Cystic Fibrosis Conference in October 2018.

“The manifestations of CF are often present at birth, which underscores our relentless commitment to reach the youngest CF patients possible in our clinical trials,” said Reshma Kewalramani, M.D., Executive Vice President and Chief Medical Officer at Vertex. “As an important outcome of these efforts, we are now able to treat infants with cystic fibrosis as early as six months of age with Kalydeco.”

Kalydeco was first approved in 2012 in the U.S. and is now available in more than 40 countries with more than 5,000 patients on therapy. For more information on Kalydeco, prescribing information, or patient assistance programs, visit Kalydeco.com or VertexGPS.com.

https://en.wikipedia.org/wiki/Ivacaftor

FDA Approves Kalydeco (ivacaftor) as First and Only CFTR Modulator to Treat Eligible Infants with CF as Early as Six Months of Age

FDA Approves Kalydeco (ivacaftor) for Cystic Fibrosis in Children Ages 12..

 Vertex Pharmaceuticals Incorporated  announced the U.S. Food and Drug Administration (FDA) approved Kalydeco (ivacaftor) to include use in children with cystic fibrosis (CF) ages 12 to <24 months who have at least one mutation in their cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to Kalydeco based on clinical and/or in vitro assay data.

“Cystic fibrosis is a chronic, progressive disease that is present at birth, with symptoms often occurring in infancy,” said Reshma Kewalramani, M.D., Executive Vice President and Chief Medical Officer at Vertex. “With today’s approval, parents and physicians now have a medicine to treat the underlying cause of CF in patients as young as one year of age. We are excited about the progress of our portfolio and continue to support additional research on the potential benefit of early intervention with all of our medicines, with the goal of bringing a treatment to all people living with CF.”

This FDA approval is based on data from the ongoing Phase 3 open-label safety study (ARRIVAL) of 25 children with CF aged 12 to <24 months who have one of 10 mutations in the CFTR gene (G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D or R117H). The study demonstrated a safety profile consistent with that observed in previous Phase 3 studies of older children and adults; most adverse events were mild or moderate in severity, and no patient discontinued due to adverse events. Two patients had elevated liver enzymes greater than eight times the upper limit of normal, but continued to receive Kalydeco after a dose interruption. The most common adverse events (≥30%) were cough (74%), pyrexia (37%), elevated aspartate aminotransferase (37%), elevated alanine aminotransferase (32%) and runny nose (32%). Four serious adverse events were observed in two patients.

Mean baseline sweat chloride for the children in this study was 104.1 mmol/L (n=14). Following 24 weeks of treatment with Kalydeco, the mean sweat chloride level was 33.8 mmol/L (n=14). In the 10 subjects with paired sweat chloride samples at baseline and week 24, there was a mean absolute change of -73.5 mmol/L. These data were presented at the 41stEuropean Cystic Fibrosis Society (ECFS) Conference in June 2018 and published in The Lancet Respiratory Medicine (Volume 6, No 7, July 2018).

“I’m very excited about the approval of ivacaftor in children ages 12 to less than 24 months as this is the first regulatory approval of a CFTR modulator in this age group,” said Margaret Rosenfeld, M.D., MPH, Seattle Children’s Research Institute and Department of Pediatrics, University of Washington School of Medicine. “The premise of newborn screening for CF is to intervene very early in the course of disease with the goal of improving long term outcomes, so this is a significant milestone for parents and caregivers of young children with CF.”

Kalydeco was already approved in the U.S. for the treatment of CF in patients ages 2 and older who have one of 38 ivacaftor-responsive mutations in the CFTR gene based on clinical and/or in vitro assay data. Vertex submitted a Marketing Authorization Application for a line extension (ages 12 to <24 months) to the European Medicines Agency with a decision anticipated in the first half of 2019.

https://es.wikipedia.org/wiki/Archivo:Carnosine.png

FDA Approves Kalydeco to Treat Rare Form of Cystic Fibrosis

The U.S. FDA approved Kalydeco (ivacaftor) for the treatment of a rare form of cystic fibrosis (CF) in patients ages 6 years and older who have the specific G551D mutation in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene. 

“Kalydeco is an excellent example of the promise of personalized medicine – targeted drugs that treat patients with a specific genetic makeup,” said FDA Commissioner Margaret A. Hamburg, M.D. “

The unique and mutually beneficial partnership that led to the approval of Kalydeco serves as a great model for what companies and patient groups can achieve if they collaborate on drug development. 

“Kalydeco is the first available treatment that targets the defective CFTR protein, which is the underlying cause of cystic fibrosis,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “This is a breakthrough therapy for the cystic fibrosis community because current therapies only treat the symptoms of this genetic disease.”

Two 48-week, placebo-controlled clinical studies involving 213 patients, one in patients ages 12 years and older and another in patients ages 6 years to 11 years, were used to evaluate the safety and efficacy of Kalydeco in CF patients with the G551D mutation. In both studies, treatment with Kalydeco resulted in significant and sustained improvement in lung function.

Kalydeco is effective only in patients with CF who have the G551D mutation. It is not effective in CF patients with two copies of the F508 mutation in the CFTR gene, which is the most common mutation that results in CF. If a patient’s mutation status is not known, an FDA-cleared CF mutation test should be used to determine whether the G551D mutation is present.

Ref : http://investors.vrtx.com/releasedetail.cfm?ReleaseID=644158